After hormone therapy trial: Confusion, mistakes and fear

When the government-funded Women’s Health Initiative study was abruptly halted in 2002, the impact was huge, swift and charged with emotion. Until the first results were released from the groundbreaking research, most doctors and older women believed that taking hormone replacement pills would protect their hearts and keep them young, healthy and hot flash-free.

Courtesy of Dr. Vivian Pinn

Dr. Vivian Pinn

Instead the hormone drugs -- to the surprise of researchers at the National Institutes of Health who had founded the study -- were shown to cause a small, but significant increase in the risk of breast cancer. Thousands of women participating in the study were instructed to stop taking the drugs, a combination of estrogen and progestin, and contact their doctors.

The findings affected millions of American women taking hormone therapy. Few doctors had clear answers for their menopausal patients because the medical community itself had been caught off guard by the results. There was plenty of frustration (Will my hot flashes return?), confusion (Was taking estrogen alone safe?) and fear (Am I at risk of heart attack, breast cancer or stroke?).

When the Women’s Health Initiative started in 1991, the 15-year randomized clinical trial was one of the largest studies of its type in the world. It was designed to compare the effects of hormone replacement therapy, vitamin D and calcium and low-fat diets on more than 160,000 women.

Women’s health pioneer Dr. Vivian Pinn, who until she retired last year was the NIH's first permanent director of the Office of Research on Women’s Health and one of the leading figures of the Women’s Health Initiative, spoke with msnbc.com about the lasting impact of the landmark study.

Q. How did the Women’s Health Initiative change the way medical science thinks about women’s health?

A. This was the first major opportunity to look at the health of women in the post-menopausal years and to determine, through a long-term randomized clinical trial, the validity of commonly used treatments to prevent the most common conditions that lead to mortality and morbidity of post-menopausal women.

One of the things we were told when the study was being designed was that it was difficult, if not impossible, to get women, especially ‘older’ women, to participate in clinical trials and research and that we would never be able to recruit that many women of post-menopausal age. [The study] really came at the beginning of current efforts to include large numbers of women in prevention studies, and the success of the recruitment helped to demonstrate that women are willing and even eager to be a part of research that may have its greatest benefits for generations to come. There had been relatively little research actually done on menopause and the post-menopausal years, especially long term studies on the menopausal transition.

Everyone had just assumed that using hormone therapy in post-menopausal women was important and valid. That was mainly because cardiovascular disease increases in post-menopausal women, and knowing that changes in blood vessels of women became more prominent after menopause when there was a decrease in estrogen levels, it seemed logical that giving estrogen to restore levels to those of the premenopausal state would then protect women from cardiovascular disease.

This study was actually designed to help us learn more about the traditional and commonly used methods to prevent the major causes of death and disability and frailty in older women, such as heart disease and stroke, cancer and fractures associated with osteoporosis, so we would know if what we as physicians were doing was scientifically appropriate. Even though women said they wanted hormone therapy for hot flashes, most physicians justified the use of hormone replacement therapy long-term on the basis of wanting to protect women from cardiovascular disease and osteoporosis.

Menopausal hormone therapy had been used for many years, but the WHI was the first long term randomized study of the risks and benefits of doing so. To have a long-term, randomized clinical trial – considered to be the “gold standard” of research -- that then showed the major basis of the practice we had been using was not valid was one of the most important and significant findings from the Women’s Health Initiative.

Q. What was the reaction to the findings in 2002?

A. There were women who were taking standard-dose estrogen or estrogen and progestin for many, many years. They said they would never stop taking them because it was keeping them young and healthy.

I can’t tell you the numbers of not very nice letters and communications that I, and others associated with the WHI, received. Women were telling me their husbands were furious with them, or they, themselves, were angry, because they ‘had to’ come off their hormones and they were now going through hot flashes again and had other symptoms.

I and another WHI investigator were at an international meeting on menopause, and there was a physician there from a European country who shook his finger in our faces, and said: ‘You are going to be the cause of women around the world losing their jobs. Because of you women won’t take their hormones so they won’t be able to work and function, all because of that study. And it’s going to be on your head.’

I’m fine with scientific questions related to the study, but many of us also experienced a lot of emotional responses from those who were just ignoring the science.

Q. Do you think there was a problem with how the 2002 results were publicly presented or reported?

A. There were misunderstandings. Even today there is confusion about menopausal hormone therapy, when not distinguishing between the results of the study of estrogen alone as opposed to estrogen and progestin combination therapy, and there is confusion about hormone use for menopausal symptoms and their use for disease prevention — the latter is what the study was about, not the former. That was not made clear in the initial reports in the news. Those reports mostly just said that hormone replacement was bad.

When you have a study that shows what both medicine and women have long accepted as being “the truth,” is wrong, you know there is going to be a reaction and there will be concern and anxiety. That was expected.

Here is what happened. The National Institutes of Health considered it important to directly inform women in the study that we were stopping the study rather than them learning about it in the press. We did not want to be seen as being responsible for continuing women in a study where the drugs they were taking might put them more at risk than giving them benefit. And, with efforts to increase the numbers of women in research studies, we wanted to make sure that these women knew they would not be exposed to increased health risks because they were in a study. For the wider population of women not in the study, our press statement advised that they should consult their physicians about stopping hormones.

And for physicians the scientific publication tried to make it clear that these findings were related to the use of hormones to prevent disease, not the use of hormones to treat hot flashes. However, doctors were unprepared to deal with this situation.

The concerns we heard from the physicians were, ‘you’re telling these people to talk to us, but we don’t know what to tell them; we’re just learning what you’re saying.’

The findings of the research were contrary to what we had been taught and thought in medical school. There was a lot of confusion about what to do and how to do it after the results were announced. There was some concern from the medical community about being caught off guard.

It was a very ‘hot’ time with calls and letters and irate physicians and concerned, anxious women. Our focus on the women was justified, but we possibly did not give enough attention to the physician community and health care community who were going to have to respond to these women’s questions. It was not easy to reconcile our desire to honor our commitment to study participants to keep them informed and do no harm, with the need to educate the medical community first.

By the time we released other parts of the study, which were much less shocking, we had developed a mechanism by which confidential information went out to different health care groups prior to press releases and journal publications. Whether that would have worked with the much more newsworthy 2002 results is of course unknown. My feeling is that it was the shocking nature of the findings, rather than the way the findings were announced, that was at the heart of the reaction.

If the results had simply confirmed what had long been thought, I doubt there would have been such uproar.

Q. Is it possible to measure the impact the Women’s Health Initiative has had, in terms of saved lives?

A. It would be almost impossible to say how many women have lived longer, how many fewer cases of breast cancer have developed because of this. There’s no way to say there’s a causal relationship, but we do know there is a parallel, that the number of breast cancer cases have been in decline in parallel with the decline in the use of hormones.

While we don’t know the actual numbers of women who have been saved from suffering some of the consequences we see associated with long-term hormone therapy, we can say, by having this kind of information, we have been able to protect women from increasing their risk of developing breast cancer, stroke and heart disease.

Q. Do you believe there will ever be an effective, safe way women can relieve menopause symptoms? Or it it something that women will just have to tough out?

A. Scientists and physicians are looking at alternative ways of administering hormones, as well as looking at alternatives to hormones. There are attempts to look at whether the skin patch is safer than taking hormones orally. Some studies show that soy does help with hot flashes. Others say it doesn’t. Many other medications and substances are being studied or suggested as alternatives to hormone therapy for symptoms that women may experience with menopause.

I have to hope there will come from research something that can be as effective as hormone therapy for preventing hot flashes and other symptoms of menopause. But I am concerned about attempting to ‘medicalize’ every aspect of normal transitions in the lives of women. We’re smart women and can recognize that a little effort on our part can make a big difference in our health.

Perhaps I can demonstrate my thoughts by alluding to results of studies for the prevention of diabetes. Studies showed that lifestyle changes could be just as effective as taking medications in preventing the development of type 2 diabetes. We’ve learned through research that you can do as much good in preventing the onset of type 2 diabetes by changing lifestyle, watching diet and exercising and losing weight as in taking a pill. We shouldn’t want to have to take a pill for everything. If we can prevent conditions and diseases by changing our own lifestyles towards healthier living, isn’t that better?